Brain tumors-Gliomas are the most frequent brain tumours in adults and, in their malignant form (grade IV or glioblastoma multiforme) remain one of the most aggressive disease with less than 5% of 5-years survival rate (Reardon et al., 2006, J. Clin. Oncol., 24, 1253). Gliomas are classified into subcategories according to their phenotypical resemblance with glial cells, mostly astrocytes (atrocytomas) and oligodendrocytes (oligodendrogliomas). Based on histopathological features, gliomas are also subdivided into low grade (grade I and II) and high grade (grade III and IV) tumors, which have distinct clinical prognosis (Reardon et al., 2006, above). Despite current advances in surgical techniques, as well as radiation and chemotherapeutical strategies, high grade gliomas remain a devastating disease with appalling prognosis. No environmental risk factors have been identified and little is known about the biological mechanisms involved in the initiation and progression phases of these brain tumours. Therefore, any significant improvement in glioma therapy or prophylaxis requests a deeper understanding of cellular and molecular mechanisms of glioma development.
The recent identification of Stem-like Cells (SC) in a number of human cancers like acute myeloid leukemias (AML), breast, ovarian and brain tumors has renewed interest in the hypothesis that cancers may arise from somatic mutations in adult stem/progenitor cells (Reya et al., 2001, Nature, 414, 105). A minor population of cancer stem-like cells may represent the source of tumor cell expansion, recurrence and metastasis, thus determining the biological behavior of tumors including proliferation, progression, and subsequently response to therapy (Reya et al., 2001, above; Galmozzi et al., 2006, Curr. Med. Chem., 13, 603). Although normal and cancer stem cells share behavioral similarities including self-renew, differentiation into multiple lineages, they differ regarding their tumorigenic potential when implanted into nude mice (Bonnet and Dick, 1997, Nat. Med. 3, 730).
Further, it is exceedingly complex to identify cancer stem marker in human gliomas that are specific for governing tumoral phenotypes. Many efforts are made to find and characterize specific cancer stem cell markers, which would discriminate them from cancer cells (markers of cells from tumor bulk) or from normal stem cells. So far, expression of CD133 was the only possibility to purify and enrich for a subpopulation of glioma stem cells showing self-renewal and tumorigenic properties (Singh et al., 2004, Nature, 432, 396). Although CD133 was described in others tumorigenic systems, it is also expressed in normal stem cells, rendering difficult the specific targeting of cancer cells for therapeutics (Yin et al., 1997, Blood, 90, 5002; Uchida et al, 2000, Proc. Natl. Acad. Sci USA, 97, 14720; Miraglia et al., 1998, Blood, 91, 4390). Moreover, it is extremely difficult to believe that only one marker would be sufficient to define “the Glioma Stem Cell Population” knowing the heterogeneity of tumor cell populations, and the current knowledge on the hematopoietic system.
There is therefore a need for new methods allowing a better selection strategy for further understanding of cellular hierarchies in gliomas and other solid cancers, notably new methods to isolate and thoroughly characterize tumor-initiating and -propagating cells showing stem cell properties, which may be useful in the treatment of such cancers.